The "standard" risk factors for coronary heart disease (CHD) appear to account for less than half of the variance in occurrence. Therefore, the overall objective of this proposal is to assess the association of immunogenetic factors with onset of CHD in white males 50 years of age or less and the interrelationship of these factors with "standard" CHD risk factors. The study population will consist of incident cases who present to the Georgia Heart Clinic at LaGrange, Georgia with CHD. The majority of these subjects will be from three counties in the mideastern section of Alabama and from counties in the midwestern section of Georgia. We will determine if there is an association of major histocompatibility complex (MHC) genetic markers HLA-A, -B, -C, -DR, C4 and BF, C3, the restriction fragment length polymorphisms (RFLP's) flanking the apolipoprotein AI and insulin genes, presence of autoantibodies, family history of CHD and/or other diseases such as diabetes and hypothyroidism, with CHD compared to healthy age, race and sex matched controls selected from the same geographic region. We will compare the frequency of these variables with "standard" CHD risk factors which will include family history, hypertension, lipid abnormalities, lifestyle, Type A behavior, obesity as well as diseases such as diabetes and hypothyroidism. All subjects selected for the study will have undergone diagnostic coronary angiography for suspected CHD. We will analyze the strength of these variables in predicting those individuals at risk for developing CHD as well as whether there are variables which predict severity of disease based on 1, 2 or 3 vessel involvement. The family members of cases and controls will be surveyed with regard to history of CHD, diabetes, hypertension and thyroid disease. This will allow one to ascertain the relative contribution of family history of these diseases in the etiology of early onset disease. Although immunogenetic factors have been suggested as risk factors for CHD, there have been no studies to specifically evaluate their contribution and the relationship with "standard" risk factors. Thus, the proposed study will utilize a well defined stable population within a relatively small geographic region in an attempt to more clearly understand risk factors for early onset CHD in white males and CHD in general.